The present invention relates to certain edible, but non-absorbable and non-digestible, liquid polyesters which can be used as low calorie fat substitutes in foods and as pharmaceutical compositions. The polyesters herein interfere with the body's absorption of cholesterol and thereby provide a means for treating hypercholesterolemia. The polyesters can undesirably interfere with the body's source of fat-soluble vitamins, but this problem is overcome by fortification with vitamins. It has now been determined that the liquid polyesters herein can also cause an undesired anal leakage effect. By the present invention, certain agents are added to the polyester/vitamin compositions to avoid this undesired effect. Highly preferred compositions for treating hypercholesterolemia and/or hyperlipidemia comprising the polyesters, an anti-anal leakage agent, and one or more fat-soluble vitamins are provided.
High blood cholesterol (hypercholesterolemia) is recognized as being a risk factor in cardiovascular disease which comprises a major health care problem today. Epidemiological studies have demonstrated that, with few exceptions, populations consuming large quantities of saturated fat and cholesterol have a relatively high concentration of serum cholesterol and a high mortality rate from coronary heart disease. While it is recognized that other factors can also contribute to the development of cardiovascular disease, there appears to be a causal relationship between the concentration of serum cholesterol, in which hypercholesterolemia results in the accumulation of undesirable amounts of cholesterol in various parts of the circulatory system (atherosclerosis) or in soft tissues (xanthomatosis), and coronary disease and coronary mortality rates.
A variety of dietary and drug regimens have been suggested for alleviating or preventing hypercholesterolemia.
By providing a fat substitute which is non-absorbable and non-digestible, the total content of cholesterol in the body can be lowered. Mineral oil is a well-known laxative and has been suggested for use as a fat substitute and as a kind of "intestinal solvent" to dissolve cholesterol and cause its removal in body wastes. However, mineral oil has never been accepted for these uses. Moreover, mineral oil is partially absorbed by the body and undesirably deposits in the liver.
In the present invention, liquid, non-absorbable, non-digestible polyesters of sugars (or sugar alcohols) are used as fat substitutes in foods and, conveniently, in unit dose forms as therapeutic compositions. The polyesters herein are fat-like in their physical properties and are excellent fat substitutes for use in low calorie foods and diets. Moreover, the polyesters herein efficiently inhibit absorption of cholesterol by the body and, in contrast with mineral oil, are not absorbed and/or deposited in the liver during usage in a treatment/prevention regimen with persons having or likely to develop hypercholesterolemia.
The polyesters herein are used in combination with fat-soluble vitamins so as to supply the body's requirement therefor.
The anal leakage effect of the liquid polyesters of the type disclosed herein can be overcome by adding an anti-anal leakage agent of the type disclosed hereinafter to the vitamin-fortified, liquid polyesters herein, or to foods containing same.
The following references are relevant to the present invention.
The copending application of Mattson, Ser. No. 628,265, filed Nov. 3, 1975, entitled COMPOSITIONS FOR INHIBITING ABSORPTION OF CHOLESTEROL, discloses vitamin-fortified liquid and solid polyesters of the general type employed herein, their use as anti-hypercholesterolemic and anti-hyperlipidemic agents, and their stool-softening laxative effect.
The concurrently-filed application of Jandacek, Ser. No. 657,528, filed Feb. 12, 1976, P&G Attorney's Docket No. 2308, entitled COMPOSITIONS FOR TREATING HYPERCHOLESTEROLEMIA, discloses binary compositions comprising a source of fatty acids and a liquid polyester of the type employed herein.
U.S. Pat. No. 3,600,186 (1971) to Mattson and Volpenhein discloses low calorie food compositions containing polyol polyesters of the general type employed herein, and their use in combination with hardstocks which are fatty acid sources. The anti-anal leakage effect of fatty acids is not noted. In a fat balance experiment, the diet fed to animals contained water-soluble vitamins, but there is no mention of fat-soluble vitamins in the polyester component of this diet.
The copending application of Mattson and Volpenhein, entitled PHARMACEUTICAL COMPOSITIONS FOR INHIBITING ABSORPTION OF CHOLESTEROL, Ser. No. 425,010, filed Dec. 14, 1973, now U.S. Pat. No. 3,954,976 discloses and claims sugar polyesters of the general type employed herein for the treatment and/or prevention of hypercholesterolemia. A variety of optional carriers are mentioned, including the fatty acid, stearic acid. The anti-anal leakage effect of stearic acid is not mentioned. The use of the disclosed polyesters in combination both with fat-soluble vitamins and fatty acids is not disclosed.
U.S. Pat. No. 1,656,474 (1928) to Dubin discloses edible fat compositions consisting of ethyl and glycerol esters of odd chain fatty acids in combination with fat-soluble vitamins.
Mattson and Nolen, The Journal of Nutrition Vol. 102, No. 9, Sept. 1972, at pages 1171-1175, report on the lack of absorbability of sugar polyesters of the general type employed herein in rats. The rats were fed water-soluble vitamins in the diet and given one drop of fat-soluble vitamins per week.
Fallet, Glueck, Mattson and Lutmer, Clinical Research XXIII No. 3 page 319A (1975) report the lowering of both serum cholesterol and vitamin A and E levels in subjects receiving sugar polyesters of the present type.
U.S. Pat. No. 2,962,419 ( 1960) to Minich relates to neopentyl fatty esters, their use as fat substitutes, and their use with "vitamins", among other things. Fat-soluble vitamins do not appear to be specifically contemplated in the Minich disclosure.
U.S. Pat. No. 3,160,565 (1964) to H. E. Duell relates to sugar mono-, di- and tri-esters and their use as carriers for various orally-administered medicinals, including the B vitamins.
U.S. Pat. No. 3,849,554 (1974) to Winitz discloses means for reducing blood serum cholesterol by ingesting diets comprising a fatty acid source, said diets being low in sucrose.
U.S. Pat. No. 2,893,990 (1959) to Hass, et al., discloses fatty acid mono- and di-esters of sucrose which aid in the absorption of fat from the digestive tract.
U.S. Pat. No. 3,158,490 (1964) to Baur and Lutton discloses non-cloudy salad oils containing esters of disaccharides in which there are not more than five unesterified hydroxy groups. See also U.S. Pat. Nos. 3,059,009 (1962) and 3,059,010 (1962) to Schmid and Baur.
U.S. Pat. No. 2,997,492 (1961) to Martin is directed to a method of making partial fatty acid esters of hexitols. U.S. Pat. No. 2,997,491 (1961) to Huber is directed to the synthesis of partial fatty esters of inositol. The general methods of synthesis disclosed in these patents can be used to prepare the liquid polyesters herein. Preferred methods of synthesis are fully disclosed hereinafter.
In addition to the foregoing, there are other patents directed to the use of fat-soluble vitamins in a variety of naturally-occurring oils not contemplated by the present invention. See, for example, U.S. Pat. No. 2,685,517, issued Aug. 3, 1954, to Nutrition Products, Inc.